Oncology Protocols Research Articles

Integrating lifestyle medicine into cancer care: A new paradigm.

179 Background: Amid rising global cancer rates and obesity-related cancer risks, oncology must blend traditional cancer treatments with evidence-based lifestyle medicine (LM) to enhance patient outcomes. LM—evidence-based interventions in nutrition, exercise, sleep, avoiding substances, and social connection —emerges as a critical tool in the care spectrum. ASCO and ACS guidelines incorporating lifestyle interventions are limited, and existing ones have notable implementation gaps. This study advocates for integration of LM into cancer care. Such interventions, supported by growing research, offer significant promise in reducing cancer treatment side effects and improving outcomes, highlighting an urgent need for their incorporation into oncological protocols. Methods: The Department of Preventive Medicine at Cleveland Clinic Abu Dhabi (CCAD) launched an LM program at the Oncology Institute. Oncologists refer to LM physicians who assess patients using an LM-validated questionnaire. Cardiometabolic risk factors: body composition, waist circumference, lipid profile, hemoglobin A1c, high-sensitivity CRP, liver function, and liver elastography are tested at baseline and 3 months. Patients receive personalized LM treatment by certified physicians, dieticians, physiatrists, and psychologists, aimed at reducing treatment side effects and enhancing cancer outcomes while improving cardiometabolic health. Follow-ups at 6 weeks and 3 months post-intervention ensure progress tracking and reassessment. Results: Initiated in January 2021, it began as a pilot program for breast cancer patients and has since expanded to all cancer patients. To date, it enrolled 425 patients, evidencing sustainability and acceptance within the patient community. Referral rates from oncologists have shown a steady increase, reflecting the program's growing credibility and utility. Patient satisfaction levels are reported to be high. Preliminary outcomes indicate improvements in both physical and psychological health metrics, suggestive of the program's comprehensive impact. Conclusions: The pioneering oncology LM program at CCAD established a transformative model that seamlessly integrates LM into traditional oncology care and acts as a bridge to survivorship. By ensuring sustained access to lifestyle interventions from the point of diagnosis through post-treatment, the program aligns with the latest research and ASCO/ACS guidelines, pioneering a new standard in cancer treatment. It can effectively address cardiometabolic risks, including obesity, and reduce treatment-related adverse outcomes. This program demonstrates the feasibility and a replicable global model, one that merges evidence-based lifestyle practices with standard oncological care to create a unified approach that could be adopted by healthcare systems worldwide, marking a significant step in the evolution of patient-centered cancer care.

The Palliative Care in Patients with Oncological Diseases - a New Medical and Therapeutic Approach

The life epectancy increase in patients with cancer requires more attention to the quality of life and mental health status of this population. The aim of the current research is to change the perspective on the evolution of oncological disorders, regardless of their localization, stage, or complications, in terms of survival chances, by eploring the essential role of psychiatric medication on the core physical and mental health-related outcomes. This is a prospective, naturalistic study, that enrolled 284 oncological patients, distributed in three groups, diagnosed with lung cancer, metastatic lung cancer or other types of cancer, who received psychotropic medication for their mood symptoms, and changes in the primary outcomes (i.e., patients’ mood and pain, and quality of the mental status of the caregivers) were monitored for si months. The results reflected the efficacy of psychopharmacological intervention initiated early after the diagnosis of cancer was formulated, according to the scores on the Integrated Palliative Care Outcome Scale (IPOS). The severity of pain, the intensity of depression, and aniety in family members decreased significantly during si months of the standard-of-care psychotropic medication administered for depressive disorders. In the long term, the objective is to change the oncological protocols to accommodate an early introduction of psychiatric medication in the evolution of oncological disease, even in the contet of moderate physical symptoms with uncertain etiology, which causes a deterioration in overall functionality and quality of life. A new notion, created by the first author, is supported by this research, i.e., “long-term oncological survivorship care,” which will replace the former concept of palliative care, which refers to “end-of-life care,” or “comfort care,” in relation to the oncological contet.

A Phyto-mycotherapeutic Supplement, Namely Ganostile, as Effective Adjuvant in Brain Cancer Management: An In Vitro Study Using U251 Human Glioblastoma Cell Line.

The current standard oncotherapy for glioblastoma is limited by several adverse side effects, leading to a short-term patient survival rate paralleled by a worsening quality of life (QoL). Recently, Complementary and Integrative Medicine's (CIM) innovative approaches have shown positive impacts in terms of better response to treatment, side effect reduction, and QoL improvement. In particular, promising potential in cancer therapy has been found in compounds coming from phyto- and mycotherapy. The objective of this study was to demonstrate the beneficial effects of a new phyto-mycotherapy supplement, named Ganostile, in the human glioblastoma cell line U251, in combination with chemotherapeutic agents, i.e., Cisplatin and a new platinum-based prodrug. Choosing a supplement dosage that mimicked oral supplementation in humans (about 1 g/day), through in vitro assays, microscopy, and cytometric analysis, it has emerged that the cells, after 48hr continuous exposure to Ganostile in combination with the chemical compounds, showed a higher mortality and a lower proliferation rate than the samples subjected to the different treatments administered individually. In conclusion, our data support the use of Ganostile in integrative oncology protocols as a promising adjuvant able to amplify conventional and new drug effects and also reducing resistance mechanisms often observed in brain tumors.

Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (OPBC-03/SAKK 23/16/IBCSG 57-18/ABCSG-53/GBG-101-TAXIS).

TPS611 Background: Axillary lymph node dissection (ALND) is standard of care for most patients with clinically node-positive breast cancer (cN+BC), either in the adjuvant setting or in case of residual nodal disease after neoadjuvant chemotherapy (NACT). At least one quarter of patients with breast cancer experience long term morbidity after ALND. The TAXIS trial was designed to investigate if axillary radiotherapy (ART) can replace ALND in patients with cN+ BC who underwent tailored axillary surgery (TAS), which is recognized as one of the most important uncertainties and controversies in axillary management of patients with breast cancer. Methods: To test the remaining indications for ALND in clinical practice, we designed the international, multicenter, phase-III, non-inferiority, randomized controlled TAXIS trial to be pragmatic (average PRECIS-2 score of 4.44). Accordingly, most study domains follow usual care conditions, including eligibility (following routine indications for ALND in clinical practice), surgical skills and techniques, and follow up. The radiation oncology protocol included detailed recommendations and an extensive quality assurance program, which was developed to address the limitations of prior landmark trials and increase acceptability among recruiters. The main objective of the trial is to demonstrate that treatment with TAS and ART is non-inferior to TAS and ALND in terms of disease-free survival (DFS) of patients with cN+ BC detected by imaging or palpation in the upfront surgery setting or in case of residual disease after NACT. Randomization at a 1:1 ratio is mainly performed intraoperatively to either use TAS followed by ALND and regional nodal irradiation excluding the dissected axilla as a target volume (arm A) or to use TAS followed by regional nodal irradiation including the full axilla (arm B). The sample size is based on the primary endpoint DFS. With a type I error of 5% and a power of 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm). The sample size was calculated to be 1500 patients (750 per arm). Enrolment started in July 2018 and will stop after reaching 1500 patients, which is expected to be completed by Q4/2025. With currently 51 active sites from Europe, Canada and Korea within the network of the Oncoplastic Breast Consortium (OPBC), >950 patients were randomized by January 2024. Another 14 sites in Europe, USA, and South America will join the trial in 2024. The interim analysis (after 20% of the required events) is expected for Q4/2024 and will be reviewed by the IDMC. The primary endpoint analysis is planned in Q4/2030. Clinical trial information: NCT03513614 .

New Benchmarks on Protocol Amendment Experience in Oncology Clinical Trials.

The drug development industry's focus on cancer-related treatments continues to rise, with narrow patient populations and complex procedures increasing the complexity of oncology protocols at an accelerated rate compared to non-oncology drugs. Tufts Center for the Study of Drug Development utilized data from a study investigating the impact of protocol amendments to compare how oncology clinical trials differ from non-oncology and identify opportunities to optimize performance in oncology clinical trials. Sixteen drug development industry companies contributed data from 950 protocols and 2,188 amendments to a study conducted in 2022 investigating protocol amendments. Analysis compared differences in amendment impact and causes between 249 oncology and 701 non-oncology protocols. Compared to non-oncology, oncology protocols had a significantly higher prevalence (72.1% and 91.1%, respectively) and number (3.0 and 4.0, respectively) of protocol amendments. Oncology protocols with amendments had significantly lower participant completion rates compared to oncology protocols without amendments, while no significant differences were found among non-oncology. During the COVID-19 pandemic, the study found an increased number of substantial amendments, lower completion rates, and higher dropout rates among oncology protocols compared to before the pandemic. Efforts to prevent avoidable protocol amendments in the industry have not been effective in oncology, where increasingly complex designs are reflected in difficult to predict cycle times, barriers to recruitment and retention and an increase in protocol amendments.

Towards Agility in Breast Cancer Treatment Principles as Adopted from Agile Software Engineering.

The complex nature of breast cancer demands flexible and adaptable principles that can account for the diverse characteristics and evolving conditions of each patient. However, there are no common breast cancer treatment agility principles that can influence policies and direct breast cancer professionals and healthcare providers into enhancing the delivery of health outcomes to patients under these conditions along with continuous rapid improvements in breast cancer treatment plan design. The incorporation of agile principles from software engineering offers a promising avenue for enhancing patient care. This research is conducted to identify breast cancer treatment agility principles adopted from the software engineering field and to validate their conformance to agility through work reported from literature in breast cancer treatment context. The authors applied a structured research methodology that involved interviews for eliciting and validating twelve agility principles from oncologists. Discussion of each principle is reflected using work reported from literature as a form of validation. Finally, a domain expert reviewed the literature-driven validation for each of the twelve identified breast cancer treatment agile principle to finally validate their conformance to agility and provide results. This work resulted twelve validated agility principles for breast cancer treatment and classified whether they are meeting, partially-(hybrid), or not meeting agility. Seven out of the twelve agile principles resulted as meeting agility, where the remaining five principles resulted as partially meeting agility. None of them is recorded as not meeting agility. The work contributes to forming an agile mindset that can empower breast cancer professionals to optimize treatment plans, enhance patient experiences, and continuously improve the quality of care. The twelve identified agile principles are anticipated to contribute to driving more efficient oncology practices, policies, and protocols. It is concluded that the breast cancer treatment agility principles are not limited to twelve.

Impact of exercise on cancer: mechanistic perspectives and new insights.

This review critically evaluates the substantial role of exercise in enhancing cancer prevention, treatment, and patient quality of life. It conclusively demonstrates that regular physical activity not only reduces cancer risk but also significantly mitigates side effects of cancer therapies. The key findings include notable improvements in fatigue management, reduction of cachexia symptoms, and enhancement of cognitive functions. Importantly, the review elucidates the profound impact of exercise on tumor behavior, modulation of immune responses, and optimization of metabolic pathways, advocating for the integration of exercise into standard oncological care protocols. This refined abstract encourages further exploration and application of exercise as a pivotal element of cancer management.

Implications of Agile Values in Software Engineering for Agility in Breast Cancer Treatment: Protocol for a Comparative Study.

Breast cancer treatment has been described as a dynamic and patient-centered approach that emphasizes adaptability and flexibility throughout the treatment process. Breast cancer is complex, with varying subtypes and stages, making it important to tailor treatment plans to each patient's unique circumstances. Breast cancer treatment delivery relies on a multidisciplinary team of health care professionals who collaborate to provide personalized care and quick adaptation to changing conditions to optimize outcomes while minimizing side effects and maintaining the patient's quality of life. However, agility in breast cancer treatment has not been defined according to common agile values and described in language comprehensible to breast cancer professionals. In the rapidly evolving landscape of breast cancer treatment, the incorporation of agile values from software engineering promises to enhance patient care. Our objective is to propose agile values for breast cancer treatment adopted and adapted from software engineering. We also aim to validate how these values conform to the concept of agility in the breast cancer context through referencing past work. We applied a structured research methodology to identify and validate 4 agile values for breast cancer treatment. In the elicitation phase, through 2 interviews, we identified 4 agile values and described them in language that resonates with breast cancer treatment professionals. The values were then validated by a domain expert and discussed in the context of supporting work from the literature. Final validation entailed a domain expert conducting a walkthrough of the 4 identified agile values to adjust them as per the reported literature. Four agile values were identified for breast cancer treatment, and among them, we validated 3 that conformed to the concept of agility. The fourth value, documentation and the quality of documentation, is vital for breast cancer treatment planning and management. This does not conform to agility. However, its nonagility is vital for the agility of the other values. None of the identified agile values were validated as partially conforming to the concept of agility. This work makes a novel contribution to knowledge in identifying the first set of agile values in breast cancer treatment through multidisciplinary research. Three of these values were evaluated as conforming to the concept of agility, and although 1 value did not meet the concept of agility, it enhanced the agility of the other values. It is anticipated that these 4 agile values can drive oncology practice, strategies, policies, protocols, and procedures to enhance delivery of care. Moreover, the identified values contribute to identifying quality assurance and control practices to assess the concept of agility in oncology practice and breast cancer treatment and adjust corresponding actions. We conclude that breast cancer treatment agile values are not limited to 4. RR1-10.2196/53124.

Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG)

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients’ sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal karyotype, FLT3-ITD, DNMT3A, NPM1 and WT1 mutations and less often complex karyotype, ASXL1, SRSF2, U2AF1, RUNX1, or KIT mutations. More women were in the 2022 European LeukemiaNet intermediate-risk group and more men in adverse-risk group. We found sex differences in co-occurring mutation patterns and prognostic impact of select genetic alterations. The mutation-associated splicing events and gene-expression profiles also differed between sexes. In patients aged <60 years, SF3B1 mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients’ sex in analyses of AML biology and prognostication.

High population frequencies of MICA copy number variations originate from independent recombination events.

MICA is a stress-induced ligand of the NKG2D receptor that stimulates NK and T cell responses and was identified as a key determinant of anti-tumor immunity. The MICA gene is located inside the MHC complex and is in strong linkage disequilibrium with HLA-B. While an HLA-B*48-linked MICA deletion-haplotype was previously described in Asian populations, little is known about other MICA copy number variations. Here, we report the genotyping of more than two million individuals revealing high frequencies of MICA duplications (1%) and MICA deletions (0.4%). Their prevalence differs between ethnic groups and can rise to 2.8% (Croatia) and 9.2% (Mexico), respectively. Targeted sequencing of more than 70 samples indicates that these copy number variations originate from independent nonallelic homologous recombination events between segmental duplications upstream of MICA and MICB. Overall, our data warrant further investigation of disease associations and consideration of MICA copy number data in oncological study protocols.

The Role of Small Nucleolar RNAs As Putative Biomarkers of Chemoresistance in Pediatric Acute Lymphoblastic Leukemia

Background Many previous studies have focused on the molecular landscape of pediatric acute lymphoblastic leukemia (ALL) with the aim to identify genetic changes related to disease development and outcome. However, the functional role of non-coding RNAs (ncRNAs) in leukemogenesis and treatment response is not fully understood. A group of ncRNAs known as small nucleolar RNAs (snoRNAs) regulates ribosomal biosynthesis, RNA splicing, and performs microRNA-like functions that affect post-translational gene expression. These functionalities can be dysregulated in cancer. The aim of this study was to explore the relationship between snoRNA expression and ex-vivo drug resistance in a cohort of pediatric ALL patients enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) protocols. Methods We analyzed 119 B-ALL patients who were treated according to two consecutive NOPHO protocols (1992 and 2000). B-cells (CD19+) and T-cells (CD3+) from healthy blood donors were used as controls (n = 10). We stratified patients into low-, medium-, and high-resistance groups by ex-vivo drug screening using 10 commonly used chemotherapeutic drugs with the fluorometric microculture cytotoxicity assay (FMCA). RNA sequencing (RNA-seq) data were generated for all patients. Pairwise comparisons (Benjamini-Hochberg (BH) corrected Mann-Whitney U test) were conducted between the low and high resistance groups to detect differentially expressed genes. We selectively retained the differentially expressed snoRNAs for downstream analysis. BH corrected Kruskal-Wallis H and Mann-Whitney U tests were performed to compare the snoRNA expression levels for the three drug resistance groups, and between the ALL and control samples, respectively. Results We identified a set of 23 unique significantly upregulated snoRNAs (p-adjusted value &amp;lt; 0.05 and absolute log2FC&amp;gt;1) in the high-resistance group for one or multiple drugs: amsacrine (ams, n = 10), etoposide (eto, n = 10), tioguanine (thio, n = 8) and mitoxantrone (mito, n = 1). Among these genes, five snoRNAs ( SNORA30, SNORA33, SNORA36C, SNORA62 and SNORA66) were overexpressed in patients resistant to ams and eto, and one snoRNA ( SNORD27) in patients resistant to ams and mito. Gene annotation revealed 22 significantly differentially expressed snoRNAs residing within the intronic region of 20 host genes, either protein coding (including ribosomal genes) or long ncRNAs. Three snoRNAs ( SNORD22-eto, SNORD26-ams and SNORD27-ams and mito) arise from the same host gene ( SNHG1). Of the 23 differentially expressed snoRNAs, the majority (n = 18) were not differentially expressed between the ALL and control samples (BH corrected Mann-Whitney U test p-value ≥ 0.05). The expression of the host genes did not differ among the resistance groups (BH corrected Kruskal-Wallis H test p-value ≥ 0.05). However, we found that 14 of the host genes were differentially expressed between the ALL samples and controls (BH corrected Mann-Whitney U test p-value &amp;lt; 0.05). Conclusions This study is one of the first to focus on the role of snoRNAs and ex-vivo drug resistance in pediatric ALL. Our findings highlight substantial variations in snoRNA expression across the three resistance groups, underscoring the potential role of snoRNAs in modulating drug response. Importantly, our analysis indicates that the differential expression of snoRNAs in the resistance groups cannot be solely attributed to host gene expression, implying that targeting pathways involving host genes might not be the most effective approach. Rather than concentrating on pathways involving host genes, our results suggest that understanding the mechanisms of action of snoRNAs could provide promising avenues for developing novel therapeutic targets to enhance drug response in pediatric ALL.

Mapping Chemo-Resistance Profiles of Pediatric Acute Leukemia through Integration of Ex-Vivo Drug Screens with Molecular Data

Introduction While novel approaches for treatment of acute lymphoblastic leukemia (ALL) in children have resulted in significant improvements in survival rates, survivors are faced with potentially life-long challenges as a result of the highly toxic treatment and the outcome for patients who relapse remains poor. The current risk-adapted treatment for ALL in children includes multiple drugs administered sequentially or in combination, with little variation in timing or intensity. Factors that affect varying treatment response between patients and cellular mechanisms that underly response to individual drugs are still under exploration. In this study, we investigate the relationship between ex-vivo drug resistance, transcriptomes, epigenomes and clinical outcome, with the aim of better understanding underlying determinants of treatment response. Methods Pediatric patients diagnosed with B-ALL between 1992 and 2008 in the Nordic countries were included in the study (n = 598). For these patients, ex-vivo drug response to ten clinically used drugs was determined using the fluorometric microculture cytotoxicity assay (FMCA). Clinical data, including follow-up information (overall survival and relapse free survival) was available for all patients. Additionally, DNA-methylation (450K array, n = 383) and gene expression profiling (RNA-seq, n = 119) was performed on a subset of diagnostic patient samples. The patients were stratified into low, medium and high resistance groups based on ex-vivo drug response. The low and high resistance groups were compared with regard to differentially methylated CpG sites or expressed genes associated with individual drug response profiles. Results Overall survival was significantly lower for patients with higher ex-vivo drug resistance to dexamethasone, doxorubicin and thioguanine compared to patients that displayed sensitivity to these drugs (p &amp;lt; 0.05). Similarly, relapse free survival was significantly lower for patients with ex-vivo resistance to cytarabine, dexamethasone, doxorubicin, prednisolone and thioguanine (p &amp;lt; 0.05). After adjusting for sex and risk group, according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) protocol, in a Cox proportional hazards model, higher hazard ratios for relapse were observed in the highly resistant group across all drugs. We identified distinct DNA methylation and gene expression patterns in patients with low and high resistance, indicating the presence of predetermined molecular resistance fates. These resistance patterns included 665 genes that were differentially expressed (absolute log2FC &amp;gt; 1, Benjamini-Hochberg adjusted p value &amp;lt; 0.05) and 1 422 CpG sites with differential methylation status (absolute mean β-value difference &amp;gt; 0.2, Benjamini-Hochberg adjusted p value &amp;lt; 0.05) in resistant compared to sensitive groups, for one or multiple drugs. With the aim of identifying the genes with the largest impact on drug resistance, we selected the most differentially expressed genes and the genes with the largest difference in methylation status between resistant and sensitive samples. Among these, we identified ~20 putative genes of interest for future studies into resistance mechanisms based on potential functional prioritization. Conclusion Our findings confirm that drug response profiles are associated with outcome in pediatric ALL, reflecting response in vivo. We show molecular evidence for differentiating low- and high-resistant types based on diagnostic gene expression and DNA methylation profiles, suggesting contribution of certain molecular signatures to drug response. Our data integrating molecular data with drug response profiles may help identifying such changes of importance in drug resistance mechanisms.

Genomic Profiles and Associated Survival Prognosticators in Black Patients with Acute Myeloid Leukemia

Background Our knowledge of the genomics of acute myeloid leukemia (AML), which serves as the basis of clinically used prognostic biomarkers and therapeutic advances (including targeted therapies), is almost exclusively based on data from patients (pts) of European ancestry. Methods We analyzed the exomes and transcriptomes of 100 Black AML pts at diagnosis who received intensive induction chemotherapy on Alliance for Clinical Trials in Oncology (Alliance) protocols. African Ancestry was confirmed by SNP analysis. We established their genetic landscape including somatic gene mutations, structural variants, gene fusions and associated gene expression. Somatic mutation frequency was compared to whole-exome sequencing of 741 White pts at diagnosis from the Beat AML cohort analyzed by identical workflow. Survival of Black pts was compared to 1,519 White pts treated on the same Alliance protocols. Multivariable analysis was used to identify clinical and molecular features associated with outcomes. Results We identified 162 recurrently mutated genes in Black AML pts. We detected different mutation frequencies for AML-associated genes based on ancestry, and mutations in genes not previously implicated in AML, including PHIP alterations in 7% of this cohort. 38 genes were mutated in 3-5% of Black pts but in &amp;lt;1% of White pts . Of the 162 recurrently mutated genes in Black pts, only 41 (25%) were recurrently mutated in White pts, while 121 genes (75%) were mutated in ≤1 White patient. Only 1/741 White AML pts did not have a mutation in at least 1/ 56 recurrently mutated AML genes assessed by clinical NGS panels. By comparison, 10% of Black pts had no mutations in these genes. Analysis of gene fusions showed recurrent, cryptic CBFA2T3 fusions in 4 pts and a recurrent GGNBP2:: MYO19 fusion involving chromosome 17 not previously described in AML in 2 pts. The CBFA2T3 fusions did not cluster with CBF-AMLs by gene expression, suggesting biological differences. t-SNE visualization of gene expression showed that Black and White AML pts clustered together by known driver mutations. We identified a t-SNE cluster enriched for pts with myelodysplasia-related (MR) mutations. Notably, Black pts in this cluster were significantly younger than White pts [50 vs 58-years (y), p=0.04], suggestive of intrinsic and/or extrinsic dysplasia-causing stressors. When matched for age, performance status and study date, Black pts had higher relapse rates (63% vs 48%, p=0.05), worse disease-free (DFS, 3-y rates, 30% vs 47%, p=0.01) and overall survival (OS, 3-y rates, 31% vs 47%, p=0.007) compared to White pts. In a multivariable analysis, MR mutations (HR=2.06, p=0.03) and mutations in NPM1 (HR=2.29, p=0.009) and NRAS (HR=1.95, p=0.04) were associated with shorter DFS. Using the recently published iScore as a proxy for inflammation, we detected an enrichment of high inflammation in Black pts harboring NPM1 mutations compared to Whites (iScore high vs low; Black, 69% vs 31%, White, 45% vs 55%; p=0.08). Furthermore, when we classified pts into LSC17 prognostic groups, only 13% of Black pts in the prognostically favorable low LSC17 group were NPM1-mutated, compared with to 38% of White pts, suggesting ancestry-associated differences in the biological impact of NPM1 mutations. Mutations in IDH1/2 associated with shorter OS (HR=1.73, p=0.05) in Black pts identifying ancestry-specific risk markers. Finally, we show that the current ELN 2022 risk stratification system can be significantly improved by including NPM1, NRAS and IDH1/2 mutations as ancestry-specific adverse risk markers for Black pts ( Figure 2). Mutations in NPM1, NRAS, and IDH1/2 were enriched in a cohort of 43 Black relapsed/refractory (R/R)-AML pts via MSK-IMPACT supporting their adverse prognostic risk in Black pts. Conclusions Our work demonstrates ancestry-related differences in the genomic profiles of AML pts and calls for additional studies of ancestry-diverse populations to understand the landscape of somatic genetic alterations in AML. Further, our results emphasize the need to include ancestry-associated variants in clinical testing panels and to refine genetic risk assessment of AML by incorporating ancestry-specific prognostic biomarkers. Support: U10CA180821, U10CA180882, U24CA196171; Clinicaltrials.gov Identifiers: NCT00048958, NCT00899223, NCT00900224. https://acknowledgments.alliancefound.org.

Secondary lesions of the mucous membrane of the oral cavity as a side effect of complex anticancer treatment: a literature review.

Today, both Ukraine and the world at large are faced with a significant number of oncological diseases with various localizations. The current state of diagnosis, prevention, early detection, and access to treatment leads to a substantial number of people in each country's healthcare system who require comprehensive cancer treatments. Modern medical and diagnosis protocols in oncology involve the usage of ionizing radiation and aggressive toxic chemotherapeutic agents which can significantly disrupt the physiology of the mucous membrane of the digestive tract during treatment, especially of the oral cavity. The most common complication of complex anticancer therapy is the development of various lesions of the oral cavity, including mucositis, which harms the patient's quality of life, limits the doses of chemotherapy and radiation therapy the patient can receive, and also negatively affects the effectiveness of complex therapy treatment. Acute oral mucositis is observed among almost 100% of treatment cases. This is a significant problem for clinical oncology as it may also reduce patient compliance with comprehensive anticancer treatment. The results indicate the presence of oral problems in 100% of patients receiving specialized antitumor chemotherapy and radiotherapy, as well as the presence of a high need for specialized dental treatment.

Outcome of two cohorts with nephroblastoma treated with consecutive International Society of Paediatric Oncology protocols in a South African paediatric oncology unit

Background. Nephroblastoma is a common childhood solid tumour in South Africa.Objective. The aim was to determine outcomes of patients diagnosed with nephroblastoma between 1990 and 2018 and compare outcomes of two cohorts treated with consecutive International Society of Paediatric Oncology (SIOP) nephroblastoma protocols.Methods. This was a retrospective, descriptive study of two cohorts in Tygerberg Hospital. Cohort 1 (1990 - 2007) was treated with theSIOP 9 and SIOP 93-01 protocols, and Cohort 2 (2008 - 2018) with the SIOP 2001 protocol. Data included demographic data (age atdiagnosis, sex), HIV status, pre- and postoperative staging, surgical complications, histological types, lymph node sampling, overallsurvival (OS) and event-free survival (EFS) with the end point two years after diagnosis.Results. There were 60 children (M:F ratio 1:1.14) in Cohort 1 with an older mean age of 42 months (interquartile range (IQR)16.25 - 56.5 months) v. 45 children (M:F ratio 1:0.8) in Cohort 2 with a mean age of 37 months (IQR 22 - 45.5 months). Cohort 2 hadmore patients with localised disease (76%) than Cohort 1 (55%) (trend towards significance p=0.076). Both cohorts had a good OS(respectively 88% and 93%) and EFS (respectively 82% and 80%). Half of Cohort 1 (50%; n=30/60) did not have lymph nodes sampledwith four subsequent relapses, significantly associated with OS (p&lt;0.001) and EFS (p=0.006). There was a significant associationbetween OS and EFS and underlying histology (respectively p=0.006 and p=0.015) for Cohort 1, but only for EFS and histology (p=0.02)for Cohort 2.Conclusion. There was good OS for children with nephroblastoma treated with consecutive SIOP protocols in a single institution inSouth Africa.

Changing the Surgical Approach to Breast Diseases During the COVID-19 Pandemic Period.

Background Postponing elective surgeries during the COVID-19 pandemic has also affected the approach to both malignant and benign breast diseases. This paper aims to share how the COVID-19 pandemic affects our approach to breast cancer, benign breast cases, and the procedures' results. Methodology A cross-sectional study was conducted in a tertiary-level public hospital in Istanbul, Turkey. We retrospectively analyzed our treatment options for patients diagnosed with breast cancer and benign breast disease in the general surgery clinic of a tertiary hospital that declared a pandemic status between March 11, 2020, and June 1, 2020. Results The number of patients who visited the breast outpatient clinic and received a diagnosis of breast cancer was 23. Among the benign diseases, no intervention was made except for abscess (eight patients, 40%) and mastitis (12 patients, 60%). Conclusions Patients with acute abscesses and mastitis were treated for both diagnostic and therapeutic purposes. Chemotherapy and hormone therapy were chosen for those diagnosed with cancer. Priority was given to oncology protocols rather than surgical approaches during the pandemic. We think that different approaches will be defined as the pandemic continues.

Comprehensive molecular profiling and deep clinical annotation of electronic health records in patients with cancer: Implementation of the Avera/Sema4 oncology and analytics protocol (ASAP) in gynecologic oncology (1255)

Comprehensive molecular profiling and deep clinical annotation of electronic health records in patients with cancer: Implementation of the Avera/Sema4 oncology and analytics protocol (ASAP) in gynecologic oncology (1255)

Avera/Sema4 oncology and analytics protocol (ASAP): Quantification of HER2 protein expression and activation status in gynecologic malignancies utilizing reverse-phase protein array (RPPA) (1267)

Avera/Sema4 oncology and analytics protocol (ASAP): Quantification of HER2 protein expression and activation status in gynecologic malignancies utilizing reverse-phase protein array (RPPA) (1267)

Modeling gamma knife radiosurgical toxicity for multiple brain metastases

Background and PurposeRadiation oncology protocols for single fraction radiosurgery recommend setting dosing criteria based on assumed risk of radionecrosis, which can be predicted by the 12 Gy normal brain volume (V12). In this study, we show that tumor surface area (SA) and a simple power-law model using only preplan variables can estimate and minimize radiosurgical toxicity. Materials and MethodsA 245-patient cohort with 1217 brain metastases treated with single or distributed Gamma Knife sessions was reviewed retrospectively. Univariate and multivariable linear regression models and power-law models determined which modeling parameters best predicted V12. The V12 power-law model, represented by a product of normalized Rx dose Rxn, and tumor longest axial dimension LAD (V12 ∼ Rxn1.5*LAD2), was independently validated using a secondary 63-patient cohort with 302 brain metastases. ResultsSurface area was the best univariate linear predictor of V12 (adjR2 = 0.770), followed by longest axial dimension (adjR2 = 0.755) and volume (adjR2 = 0.745). The power-law model accounted for 90% variance in V12 for 1217 metastatic lesions (adjR2 = 0.906) and 245 patients (adjR2 = 0.896). The average difference ΔV12 between predicted and measured V12s was (0.28 ± 0.55) cm3 per lesion and (1.0 ± 1.2) cm3 per patient. The power-law predictive capability was validated using a secondary 63-patient dataset (adjR2 = 0.867) with 302 brain metastases (adjR2 = 0.825). ConclusionSurface area was the most accurate univariate predictor of V12 for metastatic lesions. We developed a preplan model for brain metastases that can help better estimate radionecrosis risk, determine prescription doses given a target V12, and provide safe dose escalation strategies without the use of any planning software.

Evaluation of serum levels of soluble (s)L- and (s)P-selectins in endometrial cancer.

A number of reports on the role of selectin in the process of carcinogenesis, at the stage of proliferation and metastasis, have been available. The aim of the study was to analyze (s)P- and (s)L-selectin serum concentrations in women with EC and to compare these concentrations to clinical/pathological parameters and disease progression using surgical-pathological staging data. A total of 46 patients with EC and 50 healthy controls were included in the study. Serum concentrations of sL- and sP-selectins were measured in all participants. The oncologic protocol was implemented in all women from the study group. Significantly higher serum concentrations were found in EC women as compared to controls. No statistically significant differences were found between the concentrations of the soluble forms of selectins and the following parameters: histologic type of EC, histologic tumor differentiation, depth of myometrial infiltration, cervical involvement, distant metastases, vascular space invasion, and disease advancement. Slightly higher (s)P-selectin concentrations were observed in serous carcinoma, in women with cervical involvement, in the sera of women with vascular space invasion and with advanced stages of the disease. Slightly higher mean (s)P-selectin concentrations correlated with lower differentiation of the tumor. Slightly higher mean (s)P-selectin concentration was detected in the sera of women with lymph node metastases and with the serosal and/or adnexal involvement. The results were statistically insignificant, but they almost reached statistical significance. L- and P-selectins play a role in the biology of EC. The absence of an unambiguous relationship between differences in (s)L- and (s)P-selectin levels and disease advancement suggests that they do not play a vital role in tumor progression in endometrial cancer.